Exposure assessment of dairy cows to parabens using hair samples analysis.

Parabens (PBs) are used as preservatives in various products. They pollute the environment and penetrate living organisms, showing endocrine disrupting activity. Till now studies on long-term exposure of farm animals to PBs have not been performed. Among matrices using in PBs biomonitoring hair samples are becoming more and more important. During this study concentration levels of methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP) butyl paraben (BuP) and benzyl paraben (BeP) were evaluated using liquid chromatography-mass spectrometry (LC-MS) in hair samples collected from dairy cows bred in the Kyrgyz Republic. MeP was noted in 93.8% of samples (with mean concentration levels 62.2 ± 61.8 pg/mg), PrP in 16.7% of samples (12.4 ± 6.5 pg/mg) and EtP in 8.3% of samples (21.4 ± 11.9 pg/mg). BuP was found only in one sample (2.1%) and BeP was not detected in any sample included in the study. Some differences in MeP concentration levels in the hair samples depending on district, where cows were bred were noted. This study has shown that among PBs, dairy cows are exposed mainly to MeP, and hair samples may be a suitable matrix for research on PBs levels in farm animals.

Assessment of immunomodulatory effects of five commonly used parabens on human THP-1 derived macrophages: Implications for ecological and human health impacts.

Parabens are widely used as broad-spectrum anti-microbials and preservatives in food, cosmetics, pharmaceuticals, and personal care products. Studies suggest that the utilization of parabens has substantially increased over the past years, particularly during the global pandemic of coronavirus disease 2019 (COVID-19). Although parabens are generally recognized as safe by the U.S. FDA, some concerns have been raised regarding the potential health effects of parabens associated with immunotoxicity. Herein, we comprehensively investigated several key characteristics of immunotoxicants of five commonly used parabens (methyl-, ethyl-, propyl-, butyl-, and benzyl parabens) in human THP-1 derived macrophages, which are effector cells serving as a first line of host defense against pathogens and tumor immunosurveillance. The results indicate parabens, at concentrations found in humans and biota, significantly dampened macrophage chemotaxis and secretion of major pro-inflammatory cytokines (TNF-α and IL-6) and anti-inflammatory cytokine (IL-10), corroborating the mRNA expression profile. Furthermore, some parabens were found to markedly alter macrophage adhesion and cell surface expression of costimulatory molecules, CD80+ and CD86+, and significantly increase macrophage phagocytosis. Collectively, these findings heighten awareness of potential immunotoxicity posed by paraben exposure at biologically relevant concentrations, providing implications for human health and ecological risks associated with immune dysfunctions.

A sustainable and innovative method to determine parabens in body creams for exposure and risk assessment.

Methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) are among the most widely used preservatives in cosmetics, drugs, and foods. These compounds have been associated with toxic effects due to the overuse of products with parabens in their formulation. The toxicity of parabens may be correlated to endocrine disruption, owing to their ability to mimic the actions of estradiol. In this paper, a simple, sustainable, robust, and innovative dispersive liquid-liquid microextraction (DLLME) technique was developed and employed to extract these xenobiotics from body cream samples, aiming to calculate the margin of safety (MoS) to assess the risk of exposure. The validated method presented suitable linearity (r > 0.99), lower limits of detection (ranging from 0.01 to 0.04 % w/w), and satisfactory precision and accuracy (ranging from 4.33 to 10.47, and from -14.25 to 13.85, respectively). Seven of the ten analysed samples presented paraben contents within the acceptable concentration according to European legislation. The MoS value obtained for PrP (37.58) suggested its reduced safety, indicating that PrP may significantly contribute to systemic exposure resulting from the use of personal care products.

Detrimental impacts and QSAR baseline toxicity assessment of Japanese medaka embryos exposed to methylparaben and its halogenated byproducts.

Despite the theoretical risk of forming halogenated methylparabens (halo-MePs) during water chlorination in the absence or presence of bromide ions, there remains a lack of in vivo toxicological assessments on vertebrate organisms for halo-MePs. This research addresses these gaps by investigating the lethal (assessed by embryo coagulation) or sub-lethal (assessed by hatching success/heartbeat rate) toxicity and teratogenicity (assessed by deformity rate) of MeP and its mono- and di-halogen derivatives (Cl- or Br-) using Japanese medaka embryos. In assessing selected apical endpoints to discern patterns in physiological or biochemical alterations, heightened toxic impacts were observed for halo-MePs compared to MeP. These include a higher incidence of embryo coagulation (4-36 fold), heartbeat rate decrement (11-36 fold), deformity rate increment (32-223 fold), hatching success decrement (11-59 fold), and an increase in Reactive Oxygen Species (ROS) level (1.2-7.4 fold)/Catalase (CAT) activity (1.7-2.8 fold). Experimentally determined LC50 values are correlated and predicted using a Quantitative Structure Activity Relationship (QSAR) based on the speciation-corrected liposome-water distribution ratio (Dlipw, pH 7.5). The QSAR baseline toxicity aligns well with (sub)lethal toxicity and teratogenicity, as evidenced by toxic ratio (TR) analysis showing TR < 10 for MeP exposure in all cases, while significant specific or reactive toxicity was found for halo-MeP exposure, with TR > 10 observed (excepting three values). Our extensive findings contribute novel insights into the intricate interplay of embryonic toxicity during the early-life-stage of Japanese medaka, with a specific focus on highlighting the potential hazards associated with halo-MePs compared to the parent compound MeP.

Occurrence profiling, risk assessment, and correlations of antimicrobials in surface water and groundwater systems in Southwest Nigeria.

The presence of antimicrobials in water has grown into a major global health concern. This study thus focused on the presence, ecological implications, and potential health risks associated with nine antimicrobials: five antibiotics (ampicillin, chloramphenicol, ciprofloxacin, metronidazole, and tetracycline) and four parabens (methylparaben, ethylparaben, propylparaben, and butylparaben) in surface water and groundwater samples collected from three Southwestern States in Nigeria (Osun, Oyo, and Lagos States). These antimicrobials were widely detected across the three States with ciprofloxacin being the most dominant having maximum average concentrations of 189 µg L-1 and 319 µg L-1 in surface water and groundwater respectively. The range of average concentrations of antibiotics in surface water are 47.3-235 µg L-1 (Osun), 27.9-166 µg L-1 (Oyo) and 52.1-159 µg L-1 (Lagos). For groundwater, it is 35.3-180 µg L-1 (Osun), 26.5-181 µg L-1 (Oyo) and 32.3-319 µg L-1 (Lagos). The average concentrations of all parabens were 32.4-153 µg L-1, 53.4-80.1 µg L-1, and 83.2-132 µg L-1 for surface water and 46.7-55.7 µg L-1, 53-117 µg L-1, and 62.4-118 µg L-1 for groundwater in Osun, Oyo, and Lagos States respectively. Methylparaben was most frequently detected paraben with average concentrations of 153 µg L-1 and 117 µg L-1 in surface water and groundwater respectively. The measured environmental concentrations of these antimicrobials pose a significant ecological risk while those of ciprofloxacin and ampicillin pose a high health risk to all population groups studied. The average concentrations of antibiotics investigated in this study exceeded their threshold values for Predicted No-Effect Concentrations (PNEC) associated with resistance selection, except for tetracycline.

Assessment of Endocrine Disruptor Exposure in Hospital Professionals Using Hair and Urine Analyses: An Awareness Campaign.

BACKGROUND: In 2021, French public authorities initiated the fourth National Environmental Health Plan to prevent environment-related health risks. This plan primarily focuses on the sensitization of health professionals and health care institutions. Endocrine disruptors (EDs) are environmental factors associated with several adverse health effects, such as reproductive disorders, obesity, and cancer. This study aimed to conduct an awareness campaign among professionals at a general hospital center on the risks related to EDs. METHODS: Hospital professionals were directly involved in this study, and urine and hair samples were collected to determine bisphenol and paraben exposure levels. Analyses were performed using validated liquid chromatography-tandem mass spectrometry methods, enabling the simultaneous determination of bisphenols and parabens. A questionnaire on lifestyle habits was distributed to assess its relationship with the exposure profiles. Nineteen professionals were recruited for the study. RESULTS: Bisphenol A was detected in 95% of the urine samples, and the chlorinated derivatives of bisphenol A were between 16% and 63%. parabens showed detection frequencies between 37% and 100%, and methylparaben was quantified at an average concentration of 0.45 ± 0.46 ng/mL. In hair samples, bisphenols A, F, and S were detected at 95%-100%, chlorinated derivatives of bisphenol A were detected at 37%-68%, and parabens were detected at 100%. CONCLUSIONS: This awareness campaign may encourage health care institutions to adopt a policy of reducing endocrine disruptor exposure among their patients and professionals, who could be educated regarding the risks associated with EDs. Conducting a multicenter study to refine the results herein and establish a dynamic to prevent endocrine disruptor and environmental risks in health care systems would be valuable.

Grouping of esters of 4-hydroxybenzoic acid for hazard assessment.

Hazardous properties of a large number of esters of 4-hydroxybenzoic acid (parabens) have been proposed by ECHA to be assessed as a group. We recommend to restrict the grouping approach to short chain esters, i.e. methyl, ethyl, propyl and butyl paraben which are very similar in chemical structures, physicochemical properties, toxicokinetics, and hazardous properties. While these parabens show a weak estrogenicity in some in vitro or in vivo screening assays, they do not induce estrogen-receptor-mediated adverse effects in intact animals. Therefore, there is no support regarding classification and labeling of endocrine disruption or reproductive toxicity of these parabens.

Occurrence, biomagnification, and risk assessment of parabens and their metabolites in marine fish: The case study of Vietnam.

Parabens have emerged as the primary preservative of choice in numerous consumer goods, prompting growing apprehension regarding their potential for human exposure. The study employed the optimized QuEChERs sample extraction method and the UHPLC-Q-Orbitrap HRMS system to generate the initial contamination profiles of seven parabens and their four metabolites in a total of 114 fish samples found along the coastline of Vietnam. The findings of the study indicated that methylparaben was the predominant substance detected, exhibiting the highest concentration in the largehead hairtail (Trichiurus lepturus) species at 32.8 ng g-1 dry weight (dw). Additionally, the metabolites with the highest detectable concentrations in the largehead hairtail were found to be 4-HB and 3,4-DHB, with levels of 8822.0 ng g-1 dw and 3490.8 ng g-1 dw, respectively. Besides, the study reveals notable variations in paraben concentrations across three distinct regions in Vietnam, namely the Central, North, and South (Mann-Whitney U test, p < 0.05). The trophic magnification factors (TMF) for methylparaben, ethylparaben, ethyl protocatechuate, and 4-hydroxybenzoic acid exhibited values exceeding 1, indicating substantial biomagnification of these substances within the marine food web of Vietnam. Additionally, noteworthy positive associations have been observed between methylparaben and ethylparaben, as well as their respective metabolites. Based on the findings of the study, it can be concluded that there is no direct impact of seafood consumption on human health in Vietnam.

Occurrence, distribution, and risk assessment of parabens in the surface water of Terengganu River, Malaysia.

The concentration, distribution, and risk assessment of parabens were determined in the surface water of the Terengganu River, Malaysia. Target chemicals were extracted via solid-phase extraction, followed by high-performance liquid chromatography analysis. Method optimization produced a high percentage recovery for methylparaben (MeP, 84.69 %), ethylparaben (EtP, 76.60 %), and propylparaben (PrP, 76.33 %). Results showed that higher concentrations were observed for MeP (3.60 µg/L) as compared with EtP (1.21 µg/L) and PrP (1.00 µg/L). Parabens are ubiquitously present in all sampling stations, with >99 % of detection. Salinity and conductivity were the major factors influencing the level of parabens in the surface water. Overall, we found no potential risk of parabens in the Terengganu River ecosystem due to low calculated risk assessment values (risk quotient < 1). In conclusion, parabens are present in the river, but their levels are too low to pose risks to aquatic organisms.

Exposure to a mixture of non-persistent environmental chemicals and neonatal thyroid function in a cohort with improved exposure assessment.

BACKGROUND: In vitro and toxicological studies have shown that non-persistent environmental chemicals can perturb thyroid hormone homeostasis. Epidemiological studies with improved exposure assessment (i.e., repeated urine samples) are needed to evaluate effects of these compounds, individually or as a mixture, in humans. We studied the associations between prenatal exposure to non-persistent environmental chemicals and neonatal thyroid hormones. METHODS: The study population consisted of 442 mother-child pairs from the French SEPAGES mother-child cohort recruited between July 2014 and July 2017. For each participant, four parabens, five bisphenols, triclosan, triclocarban, benzophenone-3 as well as metabolites of phthalates and of di(isononyl)cyclohexane-1,2-dicarboxylate were assessed in two pools of repeated urine samples (median: 21 spot urines per pool), collected in the 2nd and 3rd trimesters of pregnancy, respectively. Thyroid stimulating hormone (TSH) and total thyroxine (T4) levels were determined in newborns from a heel-prick blood spot. Maternal iodine and selenium were assessed in urine and serum, respectively. Adjusted linear regression (uni-pollutant model) and Bayesian Kernel Machine Regression (BKMR, mixture model) were applied to study overall and sex-stratified associations between chemicals and hormone concentrations. RESULTS: Interaction with child sex was detected for several compounds. Triclosan, three parabens, and one phthalate metabolite (OH-MPHP) were negatively associated with T4 among girls in the uni-pollutant model. BKMR also suggested a negative association between the mixture and T4 in girls, whereas in boys the association was positive. The mixture was not linked to TSH levels, and for this hormone the uni-pollutant model revealed associations with only a few compounds. CONCLUSION: Our study, based on repeated urine samples to assess exposure, showed that prenatal exposure to some phenols and phthalates disturb thyroid hormone homeostasis at birth. Furthermore, both uni-pollutant and mixture models, suggested effect modification by child sex, while, to date underlying mechanisms for such sex-differences are not well understood.

Are human exposure assessment the same for non-persistent organic chemicals? -from the lens of urinary variability and predictability.

Assessment of human exposure to mixtures of non-persistent chemicals from food matrices and consumer products requires accurate characterization and estimation of their preceding exposure levels, and assessment sampling approaches for these varying chemicals remain disputable. Here, we used high-throughput targeted method to quantify urinary concentrations of 59 most common non-persistent chemicals (6 parabens, 14 bisphenols, 1 triclosan, 7 benzophenones, 2 dichlorophenols, 13 phthalate metabolites and 16 antioxidants) in 158 consecutive spot samples from 11 participants over three consecutive days, 33 samples of which were first morning voids (FMVs). We found 49 chemicals with detection frequencies over 70 % in all urine samples. Principal component analyses showed greater inter-person variations than each person's inter-day variations. Intraclass correlation coefficient (ICC) to assess the reproducibility of targeted chemicals demonstrated that regardless of sampling approaches, dichlorophenols, most parabens, benzophenones and triclosan showed moderate to high reproducibility (0.445 < ICC < 0.969), with relatively high predictive power of FMVs for 24-h collections. Notably, most phthalates, bisphenols and antioxidants showed low ICC values. Together, our work demonstrates that FMV samples may be adequate for assessing human exposure to parabens, benzophenones, triclosan and dichlorophenols, whereas multiple consecutive urine collections may be advantageous for evaluating exposure to most phthalates, bisphenols and antioxidants.

Screening of antimicrobials, fragrances, UV stabilizers, plasticizers and preservatives in sewage treatment plants (STPs) and their risk assessment in India.

Community/industrial wastewater is the prime source of anthropogenic chemicals, its treatment is often a daunting task and unaffordable for many countries. Emerging Contaminants (ECs) have been drained into wastewater after continuous use/misuse and Conventional treatments in STPs do not remove them completely. ECs including antimicrobial agents, synthetic musks, Benzotriazole UV stabilizers (BUVSs), plasticizers, and preservatives are frequently reported in environment, and cause health effects to non-target organisms. Monitoring of ECs is important to understand their status in aquatic environment. Hence, it was aimed to monitor ECs (n = 21) from 11 STPs in Tamil Nadu, India. The detection frequency of most of these analytes was >90%. Antimicrobials ranged from 247 to 22,714 ng/L and 11-14,369 ng/L in influents and effluents, respectively. The synthetic musks were in the order of Tonalide > Galaxolide > Musk Ketone. BUVSs ranged from 4 to 1632 ng/L (influents) and < LOD to 29,853 ng/L (effluents). Concentration of phthalates in influents and effluents were < LOD - 11,311 ng/L and < LOD - 17,618 ng/L, respectively. Parabens were found in the order of Prophyl > Methyl > Ethyl > Butyl in influents and Methyl > Prophyl > Butyl > Ethyl in effluents. Mass loads of ECs through STPs were found as antimicrobials > plasticizers > fragrances > BUVSs > Preservatives. This study reveals increasing usage of ECs and inadequate treatment processes at STPs in India. Also helps to adopt suitable treatment processes to remove ECs from wastewater and to reuse the wastewater.

Assessment of health risk and dose-effect of DNA oxidative damage for the thirty chemicals mixture of parabens, triclosan, benzophenones, and phthalate esters.

Humans are constantly exposed to parabens (PBs), triclosan (TCS), benzophenones (BPs), and phthalate esters (PAEs) due to the widespread existence of these chemicals in personal care products (PCPs), and the high frequency of usage for humans. Previous studies indicated each class of the above-mentioned chemicals can exhibit potential adverse effects on humans, in particular DNA oxidative damage. However, the health risk assessment of combined exposures to multiple PCPs is limited, especially the overall dose-effect of mixtures of these chemicals on DNA oxidative damage. In this study, we measured the urinary levels of 6 PBs, TCS, 8 BPs, 15 metabolites of PAEs (mono-PAEs), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) from 299 adults simultaneously. PBs, TCS, BPs, and mono-PAEs were frequently detected in urinary samples with median concentrations of 52.888, 0.737, 1.305, and 141.381 ng/ml, suggesting a broad, low-level exposure among participants. Risk assessments indicated approximately 22% and 15% of participants suffered health risks (Hazard index >1) from exposure to TCS and PAEs. The relationship between 8-OHdG levels and chemical exposure was estimated by Bayesian kernel machine regression (BKMR) models. It indicated an overall positive correlation between the mixture of these chemicals and 8-OHdG, with methylparaben and mono-benzyl phthalate contributing the most to this association. Of note, sex-related differences were observed, in which exposure to PCPs led to higher health risks and more pronounced dose-effect on DNA damage in the female population. Our novel findings reveal the health risks of exposure to low-level PCPs mixtures and further point out the overall dose-response relationship between DNA oxidative damage and PCP mixtures.

Applicability of an on-line solid-phase extraction liquid chromatography - tandem mass spectrometry for the wastewater-based assessment of human exposure to chemicals from personal care and household products.

Wastewater-based epidemiology (WBE) can be a useful complementary approach to assess human exposure to potentially harmful chemicals, including those from personal care and household products. In this work, a fully automated multiresidue method, based on on-line solid-phase extraction liquid chromatography - tandem mass spectrometry, was developed for the determination of 27 biomarkers of human exposure to selected chemicals from personal care and household products, including parabens, UV filters, phthalates and alternative plasticizers, phosphorous flame retardants/plasticizers (PFRs), and bisphenols. These biomarkers include both the parent compounds and their human metabolites. In addition, two oxidative stress biomarkers, 8-epi-prostaglandin F2α and 4-hydroxy nonenal mercapturic acid, were also considered in the study. The method was carefully optimized to tackle the challenges of analyzing compounds with different physico-chemical properties in a highly complex raw wastewater matrix, while model experiments were performed to investigate filtration losses and analyte stability. The applicability of the developed method was tested by analyzing raw wastewater from four European cities: Antwerp, Brussels (Belgium), Girona (Spain), and Zagreb (Croatia). Twenty-one biomarkers (10 parent compounds and 11 metabolites) were detected in all analyzed wastewater samples. The parent compounds with the highest mass loads were PFRs, parabens, and bisphenol S, while phthalate monoesters were the most prominent metabolites. The mass loads of most compounds were quite similar across cities, but geographic differences were observed for some biomarkers, such as metabolites of phthalates and alternative plasticizers. Exposure was then assessed for seven substances for which quantitative urinary excretion data are known. Our results indicate that safe reference values were exceeded for several contaminants, including butylated phthalates, bisphenol A, and tris(2-butoxyethyl) phosphate, particularly for toddlers. With this relatively simple method, which requires less sample manipulation, it is possible to promptly identify and monitor exposure to harmful chemicals at the population level using the WBE approach.

Comprehensive assessment of estrogenic activities of parabens by in silico approach and in vitro assays.

Parabens are ubiquitous pollutants in the environment and humans due to their wide applications in food, pharmaceuticals, and personal care products. Although the estrogenic activity of some parabens has been confirmed, the underlying mechanisms and the structure-estrogenic activity relationship are still largely unclear. Here, we systematically used in silico and in vitro approaches to investigate the estrogenic potency of typical parabens, including methyl-, ethyl-, propyl-, iso-propyl-, butyl-, iso-butyl- and benzyl-paraben. Molecular dynamics simulations and binding free energy calculations were combined to investigate the atomic-level mechanism of paraben binding to estrogen receptors (ERs). Computational analysis showed that ER were the targets of tested parabens and kept a stable agonist conformation. The calculated total binding free energies suggested that van der Waals interactions were the major driving forces for paraben-ER interaction and correlated with the structure of paraben side chains. In in vitro assays, paraben with an aromatic side chain, benzyl-paraben, showed the strongest estrogenic activity at 0.01 µM and the EC50 at 0.796 ± 0.307 µM, on par with levels commonly detected in human organs. Among tested parabens with an alkyl side chain, the estrogenicity increased as the side chain length increased from 1 to 4, but no significant difference appeared between parabens with isomeric alkyl side chains (propyl- vs isopropyl and butyl- vs iso-butylparaben). The estrogenic activity of parabens was significantly related to the calculated binding energies (R2 = 0.94, p = 0.0012), depending on the side chains of parabens. Our findings provide a significant mechanism for parabens to disrupt estrogenic function and considerations for structural optimization from the perspective of environmental protection.

Comparing in planta accumulation with microbial routes to set targets for a cost-competitive bioeconomy.

Plants and microbes share common metabolic pathways for producing a range of bioproducts that are potentially foundational to the future bioeconomy. However, in planta accumulation and microbial production of bioproducts have never been systematically compared on an economic basis to identify optimal routes of production. A detailed technoeconomic analysis of four exemplar compounds (4-hydroxybenzoic acid [4-HBA], catechol, muconic acid, and 2-pyrone-4,6-dicarboxylic acid [PDC]) is conducted with the highest reported yields and accumulation rates to identify economically advantaged platforms and breakeven targets for plants and microbes. The results indicate that in planta mass accumulation ranging from 0.1 to 0.3 dry weight % (dwt%) can achieve costs comparable to microbial routes operating at 40 to 55% of maximum theoretical yields. These yields and accumulation rates are sufficient to be cost competitive if the products are sold at market prices consistent with specialty chemicals ($20 to $50/kg). Prices consistent with commodity chemicals will require an order-of-magnitude-greater accumulation rate for plants and/or yields nearing theoretical maxima for microbial production platforms. This comparative analysis revealed that the demonstrated accumulation rates of 4-HBA (3.2 dwt%) and PDC (3.0 dwt%) in engineered plants vastly outperform microbial routes, even if microbial platforms were to reach theoretical maximum yields. Their recovery and sale as part of a lignocellulosic biorefinery could enable biofuel prices to be competitive with petroleum. Muconic acid and catechol, in contrast, are currently more attractive when produced microbially using a sugar feedstock. Ultimately, both platforms can play an important role in replacing fossil-derived products.

Cumulative risk assessment and exposure characteristics of parabens in the general Taiwanese using multiple hazard indices approaches.

Parabens, a group of endocrine disrupting chemicals (EDCs), are well known preservatives in pharmaceuticals and personal care products (PPCPs). However, studies on parabens exposure and their cumulative effects in Asian population are limited. This study aimed to identify the exposure characteristics and estimate the cumulative risk of four parabens in the general Taiwanese. We have collected urine samples including 271 adults (18-97 yrs old) and 95 minors (7-17 yrs old), from Taiwan Environmental Survey for Toxicants 2013, and analyzed for four urinary parabens including methyl (MeP)-, ethyl (EtP)-, propyl (PrP)-, and butylparaben (BuP) by using ultraperformance liquid chromatography-tandem mass spectrometry. The health-based guidance value (HBGV) and the antiandrogenic properties of parabens were used to calculate the hazard index (HI) for cumulative risk. MeP and PrP were most abundant compounds and startlingly higher than those in other countries. Adults had a higher geometric mean level of four parabens than minors (adults: MeP, 381.7; PrP, 108.6; EtP, 39.6 and BuP 6.3 ng/mL; minors: MeP, 65.7; PrP, 7.9, EtP, 2.6 and BuP 2.2 ng/mL). Participants who used a higher number of personal care products had a significantly higher risk with higher concentrations of PrP (above 75th %tile) [adjusted odds ratio (aOR): 1.79, 95 % CI: 1.01-3.15] and BuP [aOR: 1.78, 95 % CI: 1.03-3.07]. The median and 95th %tile HI (the sum of the HQs of each paraben) was as 1.10 and 4.39-fold higher than acceptable cumulative threshold (HI <1) and PrP accounted for 90 % of the HI. Our results indicate omnipresent exposure to parabens among the Taiwanese population, which might cause certain level of concerns. These significant increasing trends of HI with age dependence were observed, which mainly driven by PPCPS used. Routine survey of parabens in PPCPs and continued biomonitoring needs to be urgently addressed.

Read-across and new approach methodologies applied in a 10-step framework for cosmetics safety assessment - A case study with parabens.

Parabens are esters of para-hydroxybenzoic acid that have been used as preservatives in many types of products for decades including agrochemicals, pharmaceuticals, food and cosmetics. This illustrative case study with propylparaben (PP) demonstrates a 10-step read-across (RAX) framework in practice. It aims at establishing a proof-of-concept for the value added by new approach methodologies (NAMs) in read-across (RAX) for use in a next-generation risk assessment (NGRA) in order to assess consumer safety after exposure to PP-containing cosmetics. In addition to structural and physico-chemical properties, in silico information, toxicogenomics, in vitro toxicodynamic, toxicokinetic data from PBK models, and bioactivity data are used to provide evidence of the chemical and biological similarity of PP and analogues and to establish potency trends for observed effects in vitro. The chemical category under consideration is short (C1-C4) linear chain n-alkyl parabens: methylparaben, ethylparaben, propylparaben and butylparaben. The goal of this case study is to illustrate how a practical framework for RAX can be used to fill a hypothetical data gap for reproductive toxicity of the target chemical PP.

Methylparaben as a preservative in the development of a multi-dose HPV-2 vaccine.

The human papillomavirus (HPV) vaccine is the simplest, most economical, convenient, and effective method of preventing cervical cancer. However, the current HPV vaccine is supplied as a single-dose vial with a relatively high cost per dose, which hinders its supply to low- and middle-income countries (LMICs), where the demand for HPV vaccine is highest. Therefore, it is necessary to develop a multi-dose HPV vaccine to promote large-scale affordable vaccination in LMICs. Moreover, the addition of preservatives is required to reduce the risk of microbial contamination in multi-dose vaccines within a single vial. In this study, we investigated the effects of six preservatives on HPV 16L1 and 18L1 virus-like particles in solution, as well as the aluminum adsorption status, under normal and high-temperature conditions. Multiple methods were employed, including dynamic light scattering, differential scanning calorimetry, an in vitro relative potency assay, and an in vivo potency assay in mice. Based on the above results, four types of selected preservatives were further studied, and an antimicrobial effectiveness test was performed on the HPV-2 vaccine, which was employed as a model HPV vaccine. Finally, three preservatives were selected based on their performance to evaluate the long-term stability of the HPV-2 vaccine. The results indicated that 0.12% methylparaben is the most suitable preservative for the multi-dose HPV-2 vaccine, guaranteeing the shelf life for at least three years and meeting "B" standards for antimicrobial effectiveness. The formula developed in this study can contribute toward combating cervical cancer in LMICs.

Determination of bisphenols and parabens in cow urine distillate from India: implication of human exposure and risk assessment.

The exposures of a wide range of endocrine-disrupting chemicals to cows have been linked to diseases and are a major concern. In Indian scripts, cow urine is believed to be a treatment for many diseases. Nonetheless, exposure of bisphenols and parabens to cow urine distillates is unknown. Hence, in this study, we determined the concentration of bisphenols and parabens in commercially available cow urine distillate collected from India. The mean concentration of total bisphenols and parabens ranges from the limit of quantification (LOQ) to 149.3 ng/mL and 1479.88 ng/mL, respectively. Predominant bisphenol-F and bisphenol-A were accounted for 88.6% and 6% of total bisphenol concentration, respectively, in marketed cow urine distillate, whereas methyl and propyl parabens were dominant and accounted for 33% and 65%, respectively. The estimated mean daily intake (EDI) of bisphenol for males and females were 45.94 ng/kg-bw/day and 54.29 ng/kg-bw/day, respectively, while for parabens EDI was 455.35ng/kg-bw/day and 538.14 ng/kg-bw/day for males and females, respectively. Hazard quotient, to evaluate the potential risk of exposure, showed no risk in the studied samples. Even though the EDI results from the Monte-Carlo risk assessment analysis did not exceed the acceptable daily intake, their estrogenic actions cannot be ignored in general populations. The estrogenic activities contributed by parabens and bisphenol A measured by estradiol equivalency quotient (EEQ) ranged from 0.00033-42 pg/mL and 2.3 pg/mL, respectively. Our results revealed higher concentrations of bisphenols and parabens in cow urine distillates; hence, special attention should be given to the quality and safety of cow urine distillates. Moreover, strict guidelines should be enforced for the quality of cow urine distillates.